title: Bendamustine and rituximab in relapsed and refractory hairy cell leukemia.
abstract: OBJECTIVE
  To determine tolerability and for the first time explore efficacy of bendamustine-rituximab (BR) in multiply relapsed/refractory hairy cell leukemia (HCL), using two different dose levels of bendamustine.
  
  
  METHODS
  Patients with HCL with ≥2 prior therapies requiring treatment received rituximab 375 mg/m(2) days 1 and 15 plus bendamustine 70 (n = 6) or 90 (n = 6) mg/m(2), days 1 and 2, for six cycles at 4-week intervals.
  
  
  RESULTS
  At 70 and 90 mg/m(2)/dose of bendamustine, overall response rate was 100%, with three (50%) and four (67%) complete remissions (CR) in each respective group. Minimal residual disease (MRD) was absent in 67% and 100% of CRs, respectively. All six without MRD remain in CR at 30 to 35 (median, 31) months of follow-up. Soluble CD22 and CD25 levels decreased with all responses, with median values decreasing from 17.7 and 42 ng/mL at baseline to undetectable and 2 ng/mL after CR, respectively (P < 0.001). Of 12 patients receiving 72 cycles of BR, the most common toxicities were hematologic, including thrombocytopenia (83%), lymphopenia (75%), leukopenia (58%), and neutropenia (42%). Grade III and IV hematologic toxicity included lymphopenia and thrombocytopenia (each 75%), leukopenia (58%), and neutropenia (25%). No significant dose-related differences were detected in response or toxicity.
  
  
  CONCLUSIONS
  BR has significant activity in HCL. Bendamustine at either 70 or 90 mg/m(2)/dose was highly effective in multiply relapsed/refractory HCL and could be considered for achieving durable CRs without MRD in patients after failure of standard therapies. As it was not dose-limiting, 90 mg/m(2)/dose was chosen for future testing.
authors.affiliation: Authors' Affiliations: Laboratories of Molecular Biology and Pathology, and Metabolism Branch, National Cancer Institute, NIH, Bethesda, Maryland.
authors.forename: Mauricio
authors.initials: M
authors.lastname: Burotto
authors.forename: Maryalice
authors.initials: M
authors.lastname: Stetler-Stevenson
authors.forename: Evgeny
authors.initials: E
authors.lastname: Arons
authors.forename: Hong
authors.initials: H
authors.lastname: Zhou
authors.forename: Wyndham
authors.initials: W
authors.lastname: Wilson
authors.forename: Robert J
authors.initials: RJ
authors.lastname: Kreitman
mesh_terms: D000368:Aged; D058846:Antibodies, Monoclonal, Murine-Derived / Q000009:adverse effects / Q000627:therapeutic use*; D018906:Antineoplastic Agents, Alkylating / Q000009:adverse effects / Q000627:therapeutic use*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use; D000069461:Bendamustine Hydrochloride; D001792:Blood Platelets / Q000187:drug effects; D015496:CD4-Positive T-Lymphocytes / Q000187:drug effects; D018414:CD8-Positive T-Lymphocytes / Q000187:drug effects; D004334:Drug Administration Schedule; D005260:Female; D006801:Humans; D007155:Immunologic Factors / Q000009:adverse effects / Q000627:therapeutic use*; D007943:Leukemia, Hairy Cell / Q000188:drug therapy*; D018655:Lymphocyte Count; D008297:Male; D008875:Middle Aged; D009588:Nitrogen Mustard Compounds / Q000009:adverse effects / Q000627:therapeutic use*; D010865:Pilot Projects; D010976:Platelet Count; D012074:Remission Induction; D000069283:Rituximab; D016896:Treatment Outcome
chemical_list: D058846:Antibodies, Monoclonal, Murine-Derived; D018906:Antineoplastic Agents, Alkylating; D007155:Immunologic Factors; D009588:Nitrogen Mustard Compounds; D000069283:Rituximab; D000069461:Bendamustine Hydrochloride